Nanoparticles have been considered as promising drug delivery carriers for clinically-applicable pharmaceutics with help of their drug tolerability, circulation half-life, and delivery efficiency in the past decades. Nowadays, multi-functionalities such as sustained release, molecular targeting, and environmental reactions have been adopted for development of functionally-improved nanoparticles. Especially, response behaviors against various types of physical and chemical signals have been introduced into nanoparticles as a design strategy for rendering them release drugs when exposed to particular external stimulus. Among several environmental stimuli, pH has been widely exploited as one of the important chemical cues to design responsive nanoparticles. Most applicable target of those pH-responsive nanoparticles at cellular level is intracellular delivery of anti-cancer drugs through acidified endosomal compartments where pH level rapidly drops to under 6. Although endosomal acidification may elicit harmful effect on delivered macromolecules such as DNAs, RNAs, and proteins, it can also be utilized as a chance for their endosomal escape and effective delivery. Moreover, because overcoming the endosomal acidification has been considered as a major hurdle for many types of anti-cancer drugs to be delivered as highly concentrated manner in a cytosol of cancer cells, pH-responsive drug delivery ability of nanoparticles can be a great advantage for cancer therapy applications. Also, various kinds of pH-induced cleavage chemistries of polymeric materials and diverse formulations of nanoparticles have been applied to realize the endosomal escape and cytosolic drug release.
Metal coordination complexes have been found in many biological materials (e.g., mussel fiber, spider's fangs, and squid beak), playing major roles in their tremendous mechanical, adhesive, and frictional performances. Proteinaceous cuticles covered on mussel byssal threads are the representative example, in which metal-catecholic coordinations are discovered as a form of complex between Fe(III) and 3,4-dihydroxyphenylalanine (DOPA), and act as a key cross-linking mediator for their outstanding mechanical properties. Moreover, those Fe(III)-DOPA complexes are known to be as strong as covalent bonding, and their multiple bidentate stoichiometry can be altered by environmental pH to form mono-, bis-, and tris-Fe(III)-DOPA cross-links. Using those characteristics, mussel-inspired biomaterials containing Fe(III)-DOPA complexes with high mechanical performance and self-healing property have been developed for biomedical applications. In particular, Fe(III)-DOPA complexes have been applied to the field of synthesis of nanoparticles.
However, most of the works have been focused on exploiting Fe(III)-DOPA complexes for surface modification of metal oxide nanoparticles, introduction of stabilizing nanoparticles through the surface exposure of polyethylene glycol, and altering magnetic properties of iron oxide nanoparticles, but they have not been applied for synthesis of nanoparticles to perform environmentally sensitive drug delivery.